Clinicians need to be aware of evidence-based norms for pubertal development and menstrual function and consider menstrual bleeding as a "vital sign". The menstrual cycle is defined as the number of days that elapse from the beginning of one menstrual period through the beginning of the next. A certain degree of variability from cycle to cycle is absolutely normal, but the range is wider in adolescents than in adults. The average age of menarche (first menstruation) is 12.6 years. Menstrual cycles usually last between 21 and 45 days, with an average of 32 days. A normal duration of menstruation can range from 2 to 7-8 days, with fewer than 6 full pads or tampons per day. More than 50% of the first years' cycles are anovulatory. The onset of menarche is influenced by socio-economic level, geographic location, body mass index, genetic influences, psychological factors, chemical exposure and physical exercise.
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A 30-year-old woman (ASA II, obese) in her 40th week of a first pregnancy required epidural analgesia for labor. When the cervix had dilated to 5 cm, the epidural infusion was started with a 9-mL bolus of 0.2% ropivacaine and 50 pg of fentanyl, after a negative test dose. An infusion of 0.2% ropivacaine and 1 microg/mL of fentanyl was started at a rate of 8 mL/h. A cesarean section was required after insufficient progress was made during 8 hours of labor. Eight milliliters of 0.75% ropivacaine was administered to provide anesthesia to T4; cesarean delivery was completed without complications. Early during postoperative recovery, in addition to motor blockade of the legs, the patient experienced a right brachial plexus blockade and Horner syndrome on the same side. Both effects disappeared spontaneously (1 and 4 hours later, respectively).
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Irvalec® (elisidepsin trifluoroacetate, PM02734) is a novel marine-derived cyclic peptide belonging to the Kahaladide family of compounds, currently in clinical trials with preliminary evidence of antitumor activity. Previous studies have shown a correlation between elisidepsin sensitivity and expression of the ErbB3 receptor in a panel of NSCLC cell lines. We have studied the effect of elisidepsin on the ErbB3 pathway, characterizing the expression of all members of the ErbB (HER) family of receptors and their main downstream signaling effectors, such as Akt and MAPK. Interestingly, we observed a downregulation of ErbB3 upon elisidepsin treatment that correlates with a reduction in the Akt phosphorylation levels in the most sensitive cell lines, whereas ErbB3 levels are not affected in the less sensitive ones. Also, we observed that the basal levels of ErbB3 protein expression show a significant correlation with cell viability response against elisidepsin treatment in 14 different cell lines. Furthermore, we analyzed the combination of elisidepsin with different chemotherapeutics agents, such as cisplatin, paclitaxel and gemcitabine, in a panel of different breast (MDA-MB-435, MDA-MB-231 and MCF7), lung (HOP62, DV90 and A549) and colorectal cancer cell lines (DLD1 and HT29). IC50 values for the different drugs were tested. We observed a synergistic effect in all cell lines tested with any chemotherapeutic agent. More importantly, the two in vitro elisidepsin-resistant cell lines (MDA-MB-231 and HOP62) presented a synergistic effect in combination with cisplatin and paclitaxel, respectively. These results provide a rationale for further development of these combinations in an ongoing clinical trial.
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The unexpected, but relative letdown of the combined preventive therapy topiramate + propranolol, and the failed drug telcagepant, can induce us to a state of pessimism about the future of the treatment of migraine. Nothing could be further from the truth. Multiple studies in phase II will provide us results in the coming years on numerous drugs aimed at new and very different therapeutic targets, as new gepants, monoclonal antibody against the CGRP receptor, nitric-oxide synthase inhibitors, 5-HT (1F) receptor agonists, gap-junctions blocker tonabersat, dopamine antagonists, TRPV1 receptor antagonists, prostanoids receptor agonists, glutamate receptor antagonists, third-generation antiepileptics, melatonin receptor agonists, and orexin receptor antagonists. To these, must be added the new studies with botulinum toxin, infiltration and stimulation of occipital nerves and the spheno-palatine ganglion, stimulation of vagus nerve, transcranial magnetic stimulation, acupuncture, manual and psychological therapies. Given such diversity, it is very likely that more than one of these ongoing studies give us new therapies in the next 5 years, mainly in preventive therapy. There is no reason for discouragement.
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